Sulphonated indole derivatives and a process of their manufacture



Patented Nov. 21, 1939 UNITED STATES SULPHONATED INDOLE DERIVATIVES AND A PROCESS OF THEIR MANUFACTURE Kurt Engel, St. Louis, Ht. Rhin, France, assignor to the firm J. R. Geigy S. A., Basel, Switzerland No Drawing. Application May 12, 1937, Serial Claims.

According to this invention, new water soluble derivatives of the heterocyclic series are made by treating with a sulphonating agent under mild conditions, i. e., such that no or substantially no 5 colored by-products are formed compounds of the following general structure which contain in position 1 or 2 an aliphatic or an alicyclic substituent with more than five carbon atoms, and which may be substituted in the free positions of the benzene nucleus in any desired manner, and in the remaining free positions 1, 2 and 3 by alkyl-, aralkylor aryl-groups, and may contain a double linkage in the heterocyclic nucleus. The term alicyclic is to be understood to include substituents which are derived from aromatic groups by hydrogenation.

As parent materials to be subjected directly or indirectly to sulphonation there come into ques- 25 1 tion benzopyrroles substituted in position 1 or 2 by aliphaticor alicyclic-groups having more than five carbon atoms. These compounds which are in part new can be obtained by methods known for the production of indoles; thus they may easily be prepared by splitting off water from acylated ortho-toluidides by means of sodium alcoholate at temperatures up to about 320 0. (according to Madelung, Ber. volume 45, page 1128), or by means of sodamide at a somewhat lower temperature (according to Verley, Bull. de la Soc. Chim. 1924 and 1925 and British specification No. 303,467). However, other processes for preparing indole and its substitution products may be used with equally good results.

By catalytic hydrogenation of the indoles there are obtained products which are equally valuable as parent materials for the sulphonation. However, any other known process leading to hydrogenated indoles may be used.

Some methods of preparation of some parent materials for the sulphonation which have not hitherto been known will now be briefly indicated:

One general method consists in acylating with a carboxylic acid or a suitable derivative thereof an aromatic ortho-alkyl-substituted amine which, besides the alkyl-group in ortho-position, may contain in the benzene nucleus other substituents such as alkyl-groups and whose amino-group may be either a primary or secondary one containing In Switzerland May 14, 1936 alky1-, aralkyl-, or aryl-groups, and then subjecting the acylamide to condensation to produce the indole ring according to the usual methods.

According to whether the aliphatic or alicyclic residue of high molecular weight is to be present 5 in position 1 or 2 of the indole ring, one of the following procedures must be followed:

(1) The high molecular aliphatic or alicyclic residue is to occupy position 1 in the indole.

An aliphatic or alicyclic residue containing more than five carbon atoms is introduced into an ortho-alkyl-substituted primary amine. The manner in which the 2-position is to be substituted after the indole condensation, whether by hydrogen or by an alkyl-, an aralkylor an aryl-residue, determines the carboxylic acid which must be used for the acylation. For example, N -dodecyl-ortho-toluidine may be formylated or acetylated and the product subjected to the indole fusion; in the first case there is obtained l-dodecyl-indole, and in the second case 1-dodecyl-Z-methyl-indole. Instead of the dodecyl residue there may be introduced a mixed alkyl-group corresponding with lorol (that is the mixture of alcohols obtainable by the catalytic reduction of coco-nut fatty acids), the residue of olein-alcohol or another unsaturated alcohol, or the residue of a naphthene-alcohol, a terpenealcohol, or cyclohexanol is also applicable. If instead of a formylor acetyl-residue there is introduced a phenylacetyl-, phenoxyacetylor benzoyl-residue, there will be present in 2-position after the indole ring closure a benzyl-, phenoxymethylor phenyl-group. Instead of orthotoluidine there may be used as parent material ortho-aminoethylbenezene, metaor paraxylidine, mesidine or other homologues of the orthomethyl-aminobenzene.

(2) The high molecular aliphatic or alicyclic residue is to occupy position 2 in the indole. o

In this case one starts from an ortho-alkylsubstituted primary or secondary (alkyl-, aralkylor aryl-substituted) amine, acylates with a fatty acid of high molecular weight such as stearic acid, palmitic acid, oleic acid, hydrogenized codliver oil fatty acid, hydrogenized soya bean fatty acid, palm-nut oil fatty acid, coconut fatty acid,

acid, and the product fused with sodiumethylate. 55.

There is obtained the hitherto unknown l-benzyl- 2-undecyl-(mixed with lower and higher resi dues) -5-methyl-indole.

The following is a more precise description given in illustration of the manner of preparing the indoles, the parts being by weight:

4.6 parts of sodium are dissolved in 50 parts of absolute alcohol and distilled until half the sol- Vent used has been evaporated, whereupon 30 parts of palm-nut fatty acid ortho-toluidide are added and the whole well mixed together. Then the mixture is slowly heated to 3 l0 C. with eiiicient stirring. Ethylalcohol first distils, and after this has been expelled the reaction mixture constitutes a yellow semi-solid mass. The splitting off of water occurs at a temperature range of 290-320 C.; it is accompanied by strong foaming and is complete as soon as the melt has become quiescent, the operation requiring about half an hour. After the reaction mass has cooled it is introduced into water, acidified with acetic acid, and the indole is separated or extracted by means of an organic extracting agent, and if required is distilled in a high vacuum (boiling point -210 C. under 0.4 min. pressure).

The indole mixture thus obtained is a yellowishwhite crystalline mass having a low melting point and a fecal odour. It forms a red picrate.

The yield obtained by this method is very good,- a fact which is somewhat surprising since it was not to be expected that the acylated orthotoluidine containing a residue of high molecular weight would withstand the rather high temperature of the indole fusion with alcoholate without suffering saponification to an appreciable degree. Very good yields are likewise obtained with the use of sodamide.

If in carrying out the foregoing process instead of the ortho-toluidide of palm-nut fatty acid there is used another ortho-toluidide such as that of an unsaturated or saturated fatty acid, or a mixture thereof such as oleic acid, stearic acid, hydrogenized codliver oil fatty acid or hydrogenized soya bean fatty acid and so on, or a N-substitution product of such toluidide, for example N-benzyl stearic acid-ortho-toluidide, N- palm-nut fatty acid -N-ethyl-ortho-toluidide, l T-' acetoN-lauryl-ortho-toluidide and so on, the corresponding indoles are obtained according to the same course of reaction. They are all yellowishwhite masses and, owing to their generally nonuniform nature, resemble very closely the indole mixture above described.

By catalytic hydrogenation of the indoles, for instance with copper and hydrogen at -250 C. under a pressure of ca 200 atmospheres, it is easily possible to obtain the corresponding dihydroindole mixtures which differ physically from the parent indoles chiefly by the absence of odour and a lighter colour.

The following examples illustrate the invention, the parts being by weight unless otherwise stated, and the parts by weight and the parts by volume being related in the same manner as the kilo and the liter.

Example 1 60 parts of indole prepared from palm-nut fatty acid ortho-toluidide are gradually introduced into 60 parts of sulphuric acid monohydrate at a temperature between 10 and 20 C. whilst stirring. The solution is cooled to 5 C. and 120 parts of oleum of 26 er cent strength are allowed to drop in slowly. After the whole has been stirred for 4 hours at a temperature below 10 C. a sample withdrawn from the mixture and neutralised proves to be completely soluble in water. As soon as this is the case the reaction mixture is poured on to ice, the free sulphonic acid which is precipitated is separated and neutralised by the addition of caustic soda solution. By evaporation the sodium salt is obtained in the form of a slightly colored powder which is very easily soluble in water and forms solutions which foam strongly. The alkaline earth salts of the new product are also easily soluble in water.

A product having similar properties is obtained by causing 120 parts of monohydrate and 60 parts of oleum of 66 per cent strength to act on 60 parts of the same indole under the conditions above indicated, or by introducing 1 part of the indole into a mixture of 5 parts of monohydrate and 5 parts of chlorosulphonic acid at 10 c sstirring for 14 hours, and working up as above indicated.

Example 2 20 parts of the dihydro-indole obtained by catalytic reduction of the indole obtainable from the palm-nut fatty acid-ortho-toiuidide are introduced into 20 parts of sulphonic acid monohydrate at 10 C. whilst stirring, 40 parts of oleum of 26 per cent strength are slowly dropped in, and the whole is stirred for 6 hours at20 C. The reaction mixture is then poured on to ice, the free sulphonic acid which precipitates is separated, neutralised with alkali, and the somewhat sparingly soluble sulphonate thus precipitated is filtered and dried. There is obtained a white powder.

By adding 60 parts of the same dihydro-indole to 128 parts of monohydrate at 5 C. and dropping in slowly at 0 C., after dissolution has occurred, 60 parts of oleum of 66 per cent strength, there is obtained after 3 hours at 5 C., and working up in the above manner, a white powder which is somewhat more easily soluble in water than the product above described.

Example 3 15 parts of a-heptadecenyl-indole are introduced into a mixture of 30 parts of sulphuric acid monohydrate and 30 parts of chlorosulphonic acid at 10 C. and the whole is stirred at this temperature for 14 hours. As soon as a sample withdrawn from the mixture and neutralised is soluble in water, the reaction mass is poured on to ice and the precipitated sulphonic acid is separated and neutralised. There is obtained after evaporation a white powder which in aqueous solution has good properties of capillary activity.

A similar sulphonate is obtained by dissolving 15 parts of heptadecenyl-indole in 45 parts by Volume of ether, cautiously dropping in 45 parts of chloro-sulphonic acid, and stirring for 6 hours at 20-25" C. The product is worked up as above indicated.

Erample 4 15 parts of an indole prepared from hydrogenized cod liver oil fatty acid-benzyl-orthotoluidide are introduced gradually whilst stirring into 30 parts of sulphuric acid monohydrate at 5 C. and the mixture is stirred between 5 and 15 C. until dissolution has occurred. Then at a temperature below 5 C. 30 parts of oleum of 26 per cent. strength are slowly dropped in, the temperature is slowly allowed to rise to room temperature, and the whole is stirred for 14 hours. The reaction mixture is poured on to ice, the precipitated sulphonic acid isseparated, neutralised, and evaporated. There is "obtained a white powder having good properties of capillary activity.

Instead of the indoles of the above examples there may be used other indoles such as those disclosed above, or for example the 1-lauryl-2.3- dimethyl-indole, the 1- or 3-phenyl-2-heptadecylindole, the l-stearylor -cetyl-2-phenylindole, the indoles from benzoyl-dodecyl-o-toluidide from N-benzyl-ortho-toluidide of hydrogenized soya bean fatty acid, from the N-methylortho-toluidide of naphthenic acid, campholic acid, fencholic acid, cyclohexane-carboxylic acid or'their homologues derived from m-xylidine, mesidine or the analogues dihydroindoles thereof. properties.

The new sulphonic acids and their salts obtained as described in the foregoing examples find application as capillary active agents, especially as wetting, dispersing, emulsifying, penetrating and washing agents, and in particular for emulsifying lime soaps. They are also useful as agents for softening, dressing and so on.

What I claim is:

1. The soluble salts of the indole sulphonic acid of the following general formula wherein R is a high molecular aliphatic radical rated white to slightly colored powders, soluble in water to clear solutions with capillary active properties, suitable as wetting, dispersing, emulsifying, penetrating and washing agent and in particular for emulsifying lime soap.

2. The soluble salts of the indole sulphonic acid of the following general formula wherein R represents a high molecular aliphatic radical with more than five C-atoms, V repre- The products obtained are of quite similar being, when neutralized and evaporated a white powder, soluble in water to clear solutions with capillary active properties, suitable as wetting,

dispersing, emulsifying, penetrating and washing agent and in particular for emulsifying lime soap.

4. The soluble salt of the dihydroindole sulphonic acid of the following formula l GH -Cull Y being the radical attached to the carboxylic group in the fatty acid of palm-nut oil, said salt being, when neutralized and evaporated, a white powder, soluble in water to clear solutions with capillary active properties, suitable as wetting, dispersing, emulsifying, penetrating and washing agent and in particular for emulsifying lime soap.

5. The soluble salt of the dihydroindole sulphonic acid of the following formula CH: Hots- [TA Z being the radical attached to the carboxylic group in the fatty acid of hydrogenized cod liver oil, said salts being, when neutralized and evaporated, a white powder, soluble in water to clear solutions with capillary active properties, suitable as wetting, dispersing, emulsifying, penetrating and washing agent and in particular for emulsifying lime soap.

KURT ENGEL. 

